Orforglipron

What is Orforglipron?

Orforglipron is a new medication that uses a GLP-1 receptor agonist, much like Wegovy and Mounjaro. However, rather than relying on a weekly injection, orforglipron is taken as a simple oral pill. These medications were originally designed to treat type-2 diabetes, but trials showed an alternate use for weight loss.

Orforglipron represents a significant innovation to these medications - orforglipron belongs to a new class of small-molecule, nonpeptide compounds, meaning it can be properly digested and used by the body in an oral form. Previous versions were too chemically complex for such a route, but orforglipron allows for ease of use and better oral bioavailability than previous versions.

Not only is this more convenient than an injection, but it also allows it to be less expensive than the injection-style medications.

How Does Orforglipron Work?

Orforglipron is a glucagon-like peptide-1 (GLP-1) receptor agonist. It works by binding to your body’s GLP-1 receptors and activating them; these receptors are normally used to control your hunger, making you feel full when you eat, and slowing digestion to allow more nutrients to be drawn from the food you eat.

GLP-1 medications bind to these hormone receptors in your body and mimic the action of those hormones - in the case of GLP-1, this means slowing digestion and making you feel fuller for longer, even when you eat less food. Normally, this allows your body to regulate your glucose levels, and balance energy use.

While these treatments were originally designed to allow people with type-2 diabetes control their blood sugar, they had obvious applications for weight loss. In combination with a healthy diet and exercise, Orforglipron can make it easier for you to lose weight.

Orforglipron’s non-peptide structure means it can be delivered orally, without losing any effectiveness, making it a more patient-friendly option. Research has shown that Orforglipron keeps a high level of affinity even at lower receptor occupancy, helping to minimize the risk of adverse outcomes while still providing an effective treatment outcome.

What are the Side Effects of Orforglipron?

As with any medication, some patients may experience side effects when using Orforglipron. As orforglipron has not been licensed in the UK, we do not have a full list of side effects; however, as a GLP-1 medication, it is safe to assume it may cause some gastric effects. The most common side effects may include;

• Nausea
• Vomiting
• Diarrhoea
• Abdominal discomfort

These effects may be felt most prominently at the start of your treatment, or when you increase the dosage; they should improve as your body gets used to the medication. Clinical trials have shown that the overall safety profile of Orforglipron is comparable to that of injectable GLP-1 agonists, such as Wegovy.

Please note that these are speculative side effects; we will have a conclusive list once Orforglipron has been licensed for the UK.

In some rare cases, patients may experience more severe reactions; we advise patients to talk to their doctor or seek urgent medical help if they are concerned about these effects.

How to Take Orforglipron?

As Orforglipron has not yet been licensed in the UK, we cannot say for sure what the dosing schedule will be. As an oral pill, we expect it to be taken once a day with or without food. The dose may vary depending on whether it is being used to treat type 2 diabetes or obesity.

If you are using orforglipron for weight loss, it is important to supplement your medication with exercise and changes to your diet; without these, you may find orforglipron to be less effective than it could be.

How to Store Orforglipron

Orforglipron should be stored in its original packaging at room temperature, typically between 20°C and 25°C (68°F to 77°F).

Keep away from direct sunlight, moisture, and heat to preserve its stability and effectiveness. Ensure that the medication is stored out of reach of children and pets.

Contraindications and Interactions of Orforglipron

Do not take orforglipron if you;

• Are allergic to orforglipron, any of the other listed ingredients, or any other GLP-1 receptor agonists
• Have a history of severe gastrointestinal disorders

This treatment may have drug interaction with treatments that reduce blood sugar levels, including;

• Insulin
• Sulfonylureas

These interactions could increase the risk of hypoglycemia. Patients should inform their healthcare provider about all medications, supplements, and herbal remedies they are taking to avoid potential adverse interactions.

This list is not exhaustive and further interactions may emerge through the clinical trials - for more information about who is safe to take orforglipron, please consult the Patient Information Leaflet.

When Will Orforglipron be Available?

The manufacturer of orforglipron, Eli Lilly, expects that the medication will be approved and available by early 2026. While the final set of trials have been completed, there may be delays and unexpected issues for Eli Lilly to overcome; regulatory reviews and other issues may affect how widely available Orforglipron will be, or even if it will be licensed in the UK.

Points of Interest in Trials

1. Weight Loss Efficacy: Orforglipron has shown weight loss results comparable to those achieved with injectable GLP-1 receptor agonists.
2. Cardiovascular Benefits: Studies report significant reductions in inflammatory and cardiovascular markers, suggesting added health benefits beyond weight loss.
3. Patient Convenience: Oral dosing provides a significant advantage over injectable therapies in terms of ease of use and patient adherence.
4. Long-Term Safety: Ongoing studies aim to establish Orforglipron’s safety and tolerability over extended periods.

Summary

Orforglipron Alternatives

Some patients may find that orforglipron isn’t as effective at treating their symptoms. Here at Simple Online Pharmacy, we have a number of alternatives available, including;

• Wegovy (GLP-1 medication)
• Mounjaro (GLP-1 and GIP medication)
• Orlistat (fat-binding medication)

References

Sloop, K.W., Cox, A.L., Wainscott, D.B., White, A., Droz, B.A., Stutsman, C., Showalter, A.D., Suter, T.M., Dunbar, J.D., Snider, B.M., O’Farrell, L.S., Hewitt, N., Ruble, J.C., Padgett, L.R., Woerly, E.M., Peterson, J.A., Coskun, T., Liu, Z., Coutant, D.E. and Ai, M. (2024). The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science Translational Medicine, 16(778). doi:https://doi.org/10.1126/scitranslmed.adp5765.

Wharton, S., Blevins, T., Connery, L., Rosenstock, J., Raha, S., Liu, R., Ma, X., Mather, K.J., Haupt, A., Robins, D., Pratt, E., Kazda, C. and Konig, M. (2023). Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. The New England Journal of Medicine, 389(10). doi:https://doi.org/10.1056/nejmoa2302392.

Dutta, D., Lakshmi Nagendra, Anne, B., Kumar, M., Sharma, M. and A. B. M. Kamrul‐Hasan (2024). Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis. Obesity science & practice, [online] 10(2). doi:https://doi.org/10.1002/osp4.743.

Clinicaltrials.gov. (2025). Available at: https://clinicaltrials.gov/study/NCT06649045#more-information [Accessed 15 Jan. 2025].

Author

	Name	Ian Coakley
	Role	Content Writer
	Qual.	Dipl. Biology (Immunology)
	About	Ian joined Simple Online Pharmacy in 2021, and became their first Content Writer in 2022. He uses his experience as a writer and freelance editor to ensure Simple Online Pharmacy has a high quality of content, and aims to provide patients with the right information to make educated decisions about their healthcare.